An Australian Translational Study to Evaluate the Prognostic Role of Inflammatory Markers in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab (Avastin™)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 17
- 主要终点
- Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
研究概览
简要总结
This open-label, prospective, single-arm, multicenter study will evaluate the relationship of the markers of inflammation and progression-free survival (PFS) in participants with previously untreated metastatic colorectal cancer. The study consists of two phases: Phase A treatment: oral capecitabine plus infusional oxaliplatin (XELOX) plus bevacizumab, or modified infusional 5-fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (mFOLFOX6) plus bevacizmab administered until first disease progression. Participants will then continue with Phase B treatment: infusional 5-FU, LV and irinotecan (FOLFIRI) plus bevacizumab until second disease progression. The anticipated time on study treatment is 4 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For resected primary tumor participants, and participants with primary tumor in situ:
- •Previously untreated metastatic colorectal cancer and not a candidate for curative resection
- •World Health Organization (WHO) performance status of 0-1
- •Life expectancy of greater than or equal to (>/=) 3 months
- •Eligible for XELOX, mFOLFOX6, FOLFIRI and bevacizumab treatment in accordance with local standards of care and pharmaceutical benefits scheme guidelines
- •Additional inclusion criteria for participants with primary tumor in situ:
- •Intact primary tumor of the colon or the rectum not requiring surgical intervention prior to study start
- •Minimal or asymptomatic primary tumor
排除标准
- •Resected primary tumor participants, and participants with primary tumor in situ:
- •Previous chemotherapy for metastatic colorectal cancer
- •Previous neoadjuvant or adjuvant chemotherapy less than 6 months prior to study start
- •Radiotherapy within 28 days prior to enrollment or not recovered from a radiotherapy
- •History of non-colorectal cancer (participants are eligible if disease-free for >/=5 years and the risk of recurrence is deemed low)
- •Presence of active inflammatory bowel disease
- •History of gastrointestinal perforations
- •Peritoneal disease
- •History of significant bleeding event
- •Significant vascular disease
- •Peripheral arterial thrombosis or other thrombotic event within 6 months before study start
- •Additional exclusion criteria for participants with primary tumor in situ:
- •Prior endoscopic management of the current tumor
- •Acute diverticulitis
- •Presence of intra-abdominal abscess
- •Active gastroduodenal ulcer
研究组 & 干预措施
Bevacizumab: Phase A and Phase B
The trial will consist of 2 phases of treatment. Phase A: Participants will receive bevacizumab 7.5 mg/kg intravenous (IV) infusion on Day 1 every 3 weeks in combination with XELOX (capecitabine and oxaliplatin) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluouracil) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants will continue receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan, leucovorin, and 5-fluouracil) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment should commence within 4 weeks of the date of documented first disease progression.
干预措施: Oxaliplatin (Drug)
Bevacizumab: Phase A and Phase B
The trial will consist of 2 phases of treatment. Phase A: Participants will receive bevacizumab 7.5 mg/kg intravenous (IV) infusion on Day 1 every 3 weeks in combination with XELOX (capecitabine and oxaliplatin) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluouracil) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants will continue receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan, leucovorin, and 5-fluouracil) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment should commence within 4 weeks of the date of documented first disease progression.
干预措施: Capecitabine (Drug)
Bevacizumab: Phase A and Phase B
The trial will consist of 2 phases of treatment. Phase A: Participants will receive bevacizumab 7.5 mg/kg intravenous (IV) infusion on Day 1 every 3 weeks in combination with XELOX (capecitabine and oxaliplatin) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluouracil) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants will continue receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan, leucovorin, and 5-fluouracil) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment should commence within 4 weeks of the date of documented first disease progression.
干预措施: Bevacizumab (Drug)
Bevacizumab: Phase A and Phase B
The trial will consist of 2 phases of treatment. Phase A: Participants will receive bevacizumab 7.5 mg/kg intravenous (IV) infusion on Day 1 every 3 weeks in combination with XELOX (capecitabine and oxaliplatin) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluouracil) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants will continue receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan, leucovorin, and 5-fluouracil) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment should commence within 4 weeks of the date of documented first disease progression.
干预措施: Leucovorin (Drug)
Bevacizumab: Phase A and Phase B
The trial will consist of 2 phases of treatment. Phase A: Participants will receive bevacizumab 7.5 mg/kg intravenous (IV) infusion on Day 1 every 3 weeks in combination with XELOX (capecitabine and oxaliplatin) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluouracil) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants will continue receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan, leucovorin, and 5-fluouracil) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment should commence within 4 weeks of the date of documented first disease progression.
干预措施: 5-Fluouracil (Drug)
Bevacizumab: Phase A and Phase B
The trial will consist of 2 phases of treatment. Phase A: Participants will receive bevacizumab 7.5 mg/kg intravenous (IV) infusion on Day 1 every 3 weeks in combination with XELOX (capecitabine and oxaliplatin) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluouracil) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants will continue receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan, leucovorin, and 5-fluouracil) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment should commence within 4 weeks of the date of documented first disease progression.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
时间窗: Baseline up to disease progression, death or end of study (up to 4 years)
NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. PFS was defined as the time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (carcinoembryonic antigen \[CEA\]) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. The association between NLR (NLR less than or equal to \[≤\] 5 vs greater than \[\>\] 5) and PFS was reported as hazard ratio.
次要结局
- PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B(From the start of Phase B treatment to disease progression, death or end of study (up to 4 years))
- Time to Failure of Strategy (TFS): Overall(Baseline up to disease progression, death or end of study (up to 4 years))
- PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A(Baseline up to first disease progression, death or end of study (up to 4 years))
- Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall(Baseline up to disease progression, death or end of study (up to 4 years))
- Overall Survival (OS) From the Start of Treatment to Study Completion: Overall(Baseline until death or end of study (up to 4 years))
- Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A(Baseline up to disease progression, death or end of study (up to 4 years))
- OS: Phase B(From the start of Phase B treatment death or end of study (up to 4 years))
- Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B(From the start of Phase B treatment to disease progression, death or end of study (up to 4 years))
- Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio(Baseline up to death or end of study (up to 4 years))
- AQoL-8D Global Utility Score: Phase B(Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles])
- Survival Beyond First Disease Progression: Overall(Baseline until death or end of study (up to 4 years))
- Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall(Baseline up to disease progression, death or end of study (up to 4 years))
- Percentage of Participants Who Underwent Liver Resection: Overall(Baseline up to disease progression, death or end of study (up to 4 years))
- Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio(Baseline up to disease progression, death or end of study (up to 4 years))
- Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio(Baseline up to disease progression, death or end of study (up to 4 years))
- Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio(Baseline up to disease progression, death or end of study (up to 4 years))
- European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A(Baseline, every 8-9 weeks thereafter, end of treatment (EOT) (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles])
- EuroQol-5D Utility Score: Phase B(Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles])
- Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A(Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles])
- FACT-C Score: Phase B(Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles])
- Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A(Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles])